Sialic acid-bearing substrate (Neu5Ac)

Host sialic acid-bearing substrates are terminal carbohydrate components of glycoproteins and glycolipids found on the surface of human respiratory epithelial cells (Varki, 2008, Trends Mol Med). These molecules, primarily N-acetylneuraminic acid (Neu5Ac), serve as the primary receptors for the hemagglutinin protein of influenza and parainfluenza viruses, facilitating viral attachment and entry (Malakhov et al., 2006, Antimicrob Agents Chemother). During the viral life cycle, the viral enzyme neuraminidase cleaves these sialic acid residues to allow progeny virions to detach from the host cell and infect adjacent cells (von Itzstein, 2007, Nat Rev Drug Discov). Because of their essential role in the viral life cycle, these substrates are targeted by therapeutic agents like DAS181, a recombinant sialidase that removes the sialic acid receptors to block infection (Zenilman et al., 2015, Lancet Respir Med). Additionally, neuraminidase inhibitors like oseltamivir prevent the cleavage of these substrates, effectively trapping the virus on the cell surface and preventing spread (Moscona, 2005, N Engl J Med). Beyond viral infection, these substrates play roles in cell-cell recognition and immune system modulation. Understanding the distribution and linkage of these sialic acids, such as alpha 2-3 versus alpha 2-6 linkages, is crucial for determining host range and pandemic potential of various influenza strains (Shinya et al., 2006, Nature).

Other names

N-acetylneuraminic acidSialic acidSialyl-glycoconjugatesNeuraminic acidHost cell sialic acid receptor

Enzymatic removal of terminal sialic acid residues from host cell surfaces (by sialidases) or inhibition of viral neuraminidase to prevent the cleavage of these substrates, thereby blocking viral entry or release.